Primary objective:The objective of this randomized phase 2 study is to demonstrate efficacy of RE in terms of PFS in colorectal cancer patients with liver-only metastases who are candidates for palliative systemic treatment with capecitabine plus…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
efficacy of RE in terms of PFS in CRC patients with liver-only metastases who
are candidates for palliative systemic treatment with capecitabine plus
bevacizumab.
Secondary outcome
•safety/toxicity.
•cost-effectiveness.
•quality of life (QoL).
•overall survival.
•PFS in the subgroups of patients with and without their primary tumour in situ
Background summary
In frail/elderly patients without curative treatment options the standard
treatment is capecitabine plus an antibody against the vascular endothelial
growth factor (VEGF, i.e. bevacizumab or biosimilar), given until disease
progression or unacceptable toxicity, resulting in a median progression free
survival (PFS) of 8.5-9.2 months. Capecitabine-induced hand-foot syndrome and
diarrhoea are the most commonly occurring toxicities. Prolonged exposure to CTC
grade 2 toxicity in frail or elderly patients may already significantly impact
quality of life and daily living. Therefore, treatments with less toxicity
would be of great value for these patients.
Radioembolization (RE) is a minimally invasive treatment with administration of
radioactive microspheres into the hepatic artery via a microcatheter. Since
tumors are preferentially supplied by the hepatic artery, most microspheres get
trapped in the tumor. RE has been shown a feasible and safe procedure for the
late-line treatment of unresectable CRC liver metastases. These data compare
favorably with the toxicity data of capecitabine plus bevacizumab, but this
should be validated in a prospective study in first-line.
The proposed study investigates the efficacy of RE as an alternative, better
tolerated and more cost-effective treatment option in elderly or frail patients
compared to chronic systemic treatment with comparable progression-free
survival.
Study objective
Primary objective:
The objective of this randomized phase 2 study is to demonstrate efficacy of RE
in terms of PFS in colorectal cancer patients with liver-only metastases who
are candidates for palliative systemic treatment with capecitabine plus
bevacizumab.
Secondary objectives:
• To evaluate safety/toxicity.
• To evaluate cost-effectiveness.
• To evaluate quality of life (QoL).
• To evaluate overall survival.
• To evaluate PFS in the subgroups of patients with and without their primary
tumour in situ
Study design
Multi-center, interventional, treatment, randomized phase 2, open label,
comparative study. The study will be conducted within the network of the Dutch
Colorectal Cancer Group (DCCG).
Intervention
Individualized 166Ho-RE will be performed via a catheter during angiography.
Dosimetry-based treatment planning will be individualized using Q-Suite*
software. The comparator, standard systemic treatment, will be given by the
local investigator and will consist of capecitabine orally 1000 mg/m2 bid day
1-14 + anti-VEGF antibody i.v. 7.5 mg/kg day 1 at 3-weekly cycles, continued
until disease progression or unacceptable toxicity.
Study burden and risks
It is hypothesized that treatment with radioactive microspheres will have
comparable efficacy in terms of PFS and will reduce toxicity and improve
quality of life relative to standard treatment. It is anticipated that the
gamma (γ) emission of the radioactive holmium-166 (166Ho) will ensure the
safety of the procedure by enabling pre-treatment distribution analysis after
scout dose imaging and subsequent dosimetry-based individualized treatment
planning.
In general, common adverse events after receiving radioactive microspheres to
the liver are fever, abdominal pain, nausea, vomiting, and fatigue. These
adverse events are all part of the so-called post-RE syndrome. An abnormality
of liver function tests is also likely to occur, without direct clinical
relevance. In general, these effects are transient.
Apart from the angiographic procedures and the RE related toxicity, standard
radiological and nuclear procedures are also used, which may have inherent side
effects.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
4.2 Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
1. Patients must have given written informed consent.
2. Female or male patients aged >=18 years.
3. Metastatic colorectal cancer, with metastases confined to the liver,
previously not systemically treated.
4. Elderly/frail patients, according to the local investigator not eligible for
local treatments or intensive systemic regimens with combination chemotherapy.
5. ECOG Performance status 0-2
6. Eligible for systemic treatment with capecitabine + anti-VEGF antibody.
7. Adequate bone marrow (Hb >= 6 mmol/L, WBC >= 3x109/L, platelets >= 100x109/L),
liver (serum bilirubin <= 1x upper limit of normal (ULN), Albumin >= 30 g/L,
/ALAT <= 5x (ULN), and renal (GFR >= 40 ml/min) functions.
Exclusion criteria
4.3 Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
1. Previous systemic treatment for metastatic disease.
2. Previous adjuvant treatment completed within 6 months prior to randomization.
3. Symptoms of primary tumor, if in situ, that require intervention; prior
treatment with (chemo)radiotherapy and/or resection of primary tumor is
allowed.
4. Eligible for more intensive systemic regimens (i.e. doublet or triplet
chemotherapy).
5. Eligible for other local treatment of liver metastases (e.g. surgical
resection, ablation).
6. Presence of extrahepatic metastases; the presence of small (<= 1 cm) lesions
outside the liver on CT scan that are not clearly suspicious for metastases
and/or the presence of enlarged hilar lymph nodes in the liver up to a maximal
diameter of 2 cm is allowed.
7. Non-correctable INR >2.0.
8. Any serious and/or chronic liver disease preventing the safe administration
of radioembolization
9. Any serious comorbidity preventing the safe administration of anti-VEGF
antibody treatment. This includes uncontrolled hypertension or treatment with
>=3 antihypertensive drugs, arterial (cerebro)vascular event within the past 12
months, history of bleeding, history of GI perforation, or presence of
fistulae.
10. Pregnancy or breastfeeding.
11. Mental disorders that may compromise patient compliance.
12. Concurrent second malignancy or cancer diagnosed within two years, with the
exception of tumors with low risk of systemic relapse (systemic relapse risk of
<10% over 2 years, such as adequately treated basal cell carcinoma of skin and
low risk prostate cancer). If patients have a second malignancy, liver
metastases need histological confirmation of CRC origin.
13. Body weight over 150 kg (because of maximum table load).
14. Known severe allergy for intravenous contrast fluids.
15. Actual or planned participation to another investigational study which may
compromise any endpoint of the study. This also applies to any intervention
that may influence quality of life.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05092880 |
| CCMO | NL77263.041.21 |